In hypertension as well as normotension, the principal factor protecting brain from malignant cerebral edema, hemorrhagic infarction, and stroke is the vascular system responsible for cerebral autoregulation. Our long- term goal is to develop methods, to better treat abnormalities of this vascular system, based on a batter understanding of the cellular mechanisms underlying its short and long-term modulation. This proposal derives form our recent observation that expression of functional Ca channels in cerebral vascular smooth muscle cells may be up or down- regulated in vivo, and from our recent discovery of a new cationic channel in cerebral smooth muscle that can serve as a powerful depolarizing force that would augment vascular tone. The principal hypotheses underlying this proposal are that the shape of the cerebral autoregulation curve depends on ion channels in smooth muscle cells, and the shift to the right of the autoregulation curve that occurs with hypertension reflects altered expression of ion channels in smooth muscle cells. The main goal of this grant is to compare expression of functional channels, including Ca channels, the new cationic channel and Kca channels, in smooth muscle cells from cerebral precapillary arterioles and from middle cerebral arteries from normal and from hypertensive rats (Goldblatt model). Secondary goals, designed to serve as essential controls for the main goal, include characterizing the voltage dependent properties of the channels as well as their modulation by nitric oxide and angiotensin II. Knowledge gained from these studies will be directly relevant to treatment of patients when cerebral autoregulation is abnormal, including in stroke, arteriovenous malformation and head trauma.